The present invention is directed to a method for preparing a carbamate from a compound containing an amine group.
Carbamates have been used as a blocking group for the amino function of xcex1-amino acids since the benzyloxycarbonyl group was used in 1932 by Bergmann and Zervas. Traditionally, the most important route for the synthesis of carbamates involves the use of phosgene/isocyanate technology. However, given the toxicity of phosgene and the environmental concerns associated therewith, a safer and more convenient method of providing a carbamate blocking group has been sought.
Recently, carbon dioxide has been proposed as an alternative for phosgene in the production of carbamates from amines. Carbon dioxide has been used to prepare carbamates with amines in the presence of electrophiles such as 2-bromoalkaphenols, epoxides, alkyl halides and alkynes. Recently, carbamates have been prepared using amines, carbon dioxide at a pressure of from 80 to 160 psig, alkylchlorides and sterically hindered organic bases such as pentaalkylguanidines. Rossi et al in J.Org.Chem. 1998, 63, 1337, reported a mild procedure for synthesizing carbamates through the reaction of amines and alkyl halides in the amount of five equivalents with tetraethylammonium hydrogen carbonate, prepared from tetraethylammonium hydroxide and carbon dioxide. However, this reaction was very sluggish and required the amount of five equivalents of the alkyl halide. Therefore, there still exists a need for a method for preparing carbamates from amines which is safe, economical and capable of producing carbamates in an efficient manner.
The present invention is directed to a method for preparing a carbamate from a compound containing an amine group in which the compound is reacted with an alkylating agent in the presence of carbon dioxide and cesium carbonate. In the inventive method, the reaction can take place at ambient or standard temperatures and pressures to produce the desired carbamate at a high yield without the use of dangerous phosgene gas.
The present invention provides a safe and simple method for attaching a carbonate group to amines and amino acids and for preparing other carbamates by reacting a primary or secondary amine group with carbon dioxide, cesium carbonate and an alkylating group at ambient temperature and pressure. The reaction preferably takes place in a polar aprotic solvent such as dimethylformamide and, unexpectedly, high yields of the carbamate product are obtained when cesium carbonate is present in the reaction system. The compound containing the amine group is not especially limited and can be an amino acid or any other organic compound containing at least one of a primary or a secondary amine group. Likewise, the alkylating agent is not especially limited and can be an organic compound containing a halide such as benzylchloride or chioromethyl pivalate. In the present invention, the presence of cesium carbonate in the reaction system enables the product carbamate compound to be obtained in a high yield with a low amount of by-product formation.
The advantages of the present invention are further exemplified by the following Examples and Comparative Examples.